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Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene and Arterial Oxygen Saturation at High Altitude

UCL Centre for Cardiovascular Genetics, Rayne Institute; Department of Paediatrics, Imperial College School of Medicine, St. Mary's Hospital; and Department of Clinical Pharmacology, St. Bartholomew's and the Royal London MDS, London, United Kingdom

Correspondence and requests for reprints should be addressed to Major David Woods, Department of Medicine, Level 6, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK. E-mail: doctordrwoods{at}aol.com

There is a significant genetic influence on arterial oxygen saturation (Sa_O2) in high-altitude (HA) residents. It is not known whether this is true of lowlanders ascending to HA. The I allele of the angiotensin-converting enzyme (ACE) gene is associated with low ACE activity and elite endurance performance. An excess of the I allele has also been reported in South American natives living over 3,000 m and among elite HA mountaineers who demonstrate extreme endurance in a hypoxic environment, where maintenance of Sa_O2 is crucial to performance. We postulated that the I allele may confer an advantage at HA through genotype-dependent alterations in Sa_O2. Rapid ascent (n = 32) and slow ascent groups (n = 40), ascending to approximately 5,000 m over 12.0 and 18.5 days, respectively, had their Sa_O2 assessed throughout and compared with their ACE genotype. Resting Sa_O2 was independent of the ACE genotype and remained so for the slow ascent group, in whom the fall in Sa_O2 with ascent was genotype independent. However, Sa_O2 with ascent was significantly associated with the ACE genotype in the rapid ascent group (p = 0.01) with a relatively sustained Sa_O2 in the II subjects. These data are the first to report an association of the I allele with the maintenance of Sa_O2 at HA.

Key Words: angiotensin-converting enzyme • polymorphism • altitude • oxygen saturation

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